University of Louisville

Poster Title

Mechanistic Insight Into Vinyl Chloride-Induced Liver Injury: Role of Dietary Fatty Acids

Institution

University of Louisville

Abstract

Vinyl chloride (VC) is a relevant chemical toxicant and an important occupational/environmental pollutant. Most studies on the risk of VC exposure to human health have focused on the effect of VC alone (high doses) and not taken into consideration VC interactions (low doses) with riskmodifying factors. It has been shown that certain dietary fats such as polyunsaturated fatty acids (PUFA), linoleic acid (LA) in particular, exacerbate fatty liver diseases. The purpose of the current study was to determine the role of LA metabolites in sensitizing the liver to VC via molecular, organelle, and cellular effects.Mice were administered a bolus dose of chloroethanol (or vehicle) 10 wks after being fed a linoleic acid rich high fat diet (HPUFA; 42% corn oil)-fed or low fat control diet (LPUFA; 13% corn oil). Animals were sacrificed 0-24 hours after ClEtOH exposure. Samples were harvested for determination of liver damage, inflammation, oxidative and ER stress.In LFD-fed control mice, chloroethanol caused no detectable liver damage or inflammation. In HPUFA-fed mice, chloroethanol increased HPUFA-induced liver damage, steatosis, infiltrating inflammatory cells and hepatic expression of proinflammatory cytokines and genes affected in ER stress. Furthermore, chloroethanol altered protein expression of genes involved in ER stress.Together, VC and HPUFA cause liver damage, inflammation and ER stress markers. This serves as proof-of-concept that VC hepatotoxicity may be modified by a linoleic acid rich diet. These data implicate exposure to VC as a risk factor in the development of liver disease in susceptible populations. National Cancer Institute grant R25-CA134283.

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Mechanistic Insight Into Vinyl Chloride-Induced Liver Injury: Role of Dietary Fatty Acids

Vinyl chloride (VC) is a relevant chemical toxicant and an important occupational/environmental pollutant. Most studies on the risk of VC exposure to human health have focused on the effect of VC alone (high doses) and not taken into consideration VC interactions (low doses) with riskmodifying factors. It has been shown that certain dietary fats such as polyunsaturated fatty acids (PUFA), linoleic acid (LA) in particular, exacerbate fatty liver diseases. The purpose of the current study was to determine the role of LA metabolites in sensitizing the liver to VC via molecular, organelle, and cellular effects.Mice were administered a bolus dose of chloroethanol (or vehicle) 10 wks after being fed a linoleic acid rich high fat diet (HPUFA; 42% corn oil)-fed or low fat control diet (LPUFA; 13% corn oil). Animals were sacrificed 0-24 hours after ClEtOH exposure. Samples were harvested for determination of liver damage, inflammation, oxidative and ER stress.In LFD-fed control mice, chloroethanol caused no detectable liver damage or inflammation. In HPUFA-fed mice, chloroethanol increased HPUFA-induced liver damage, steatosis, infiltrating inflammatory cells and hepatic expression of proinflammatory cytokines and genes affected in ER stress. Furthermore, chloroethanol altered protein expression of genes involved in ER stress.Together, VC and HPUFA cause liver damage, inflammation and ER stress markers. This serves as proof-of-concept that VC hepatotoxicity may be modified by a linoleic acid rich diet. These data implicate exposure to VC as a risk factor in the development of liver disease in susceptible populations. National Cancer Institute grant R25-CA134283.